Spatio-temporal electroencephalographic power distribution in experimental pigs receiving propofol.

INTRODUCTION: When assessing the spatio-temporal distribution of electroencephalographic (EEG) activity, characteristic patterns have been identified for several anesthetic drugs in humans. A shift in EEG power from the occipital to the prefrontal regions has been widely observed during anesthesia induction. This has been called "anteriorization" and has been correlated with loss of consciousness in humans. The spatio-temporal distribution of EEG spectral power in pigs and its modulation by anesthetics have not been described previously. The aim of the present study was to analyze EEG power across an anterior-posterior axis in pigs receiving increasing doses of propofol to 1) characterize the region of highest EEG power during wakefulness, 2) depict its spatio-temporal modification during propofol infusion, and 3) determine the region demonstrating the most significant modulations across different doses administered. MATERIALS AND METHODS: Six pigs with a body weight of 33.3 ± 3.6 kg and aged 11.3 ± 0.5 weeks were included in a prospective experimental study. Electroencephalographic activity was collected at the occipital, parietal and prefrontal regions at increasing doses of propofol (starting at 10 mg kg-1 h-1 and increasing it by 10 mg kg-1 h-1 every 15 minutes). The EEG power was assessed using a generalized linear mixed model in which propofol doses and regions were treated as fixed effects, whereas pig was used as a random effect. Pairwise comparisons of marginal linear predictions were used to assess the change in power when the specific propofol dose (or region) was considered. RESULTS: During both wakefulness and propofol infusion, the highest EEG power was located in the prefrontal region (p<0.001). The EEG power, both total and for each frequency band, mostly followed the same pattern, increasing from awake until propofol 20 mg kg-1 h-1 and then decreasing at propofol 30 mg kg-1 h-1. The region showing the strongest differences in EEG power across propofol doses was the prefrontal. CONCLUSION: In juvenile pigs receiving increasing doses of propofol, the prefrontal region showed the highest EEG power both during wakefulness and propofol administration and was the area in which the largest frequency-band specific variations were observed across different anesthetic doses. The assessment of the spectral EEG activity at this region could be favorable to distinguish DoA levels in pigs.

The effect of methylphenidate on anaesthesia recovery: An experimental study in pigs.

INTRODUCTION: Due to the lack of specific antagonists for general anaesthetics, the pharmacological stimulation of the arousal pathways might contribute to reduce recovery time. We aimed at assessing the effect of methylphenidate on physiological parameters, nociceptive withdrawal reflex thresholds, electroencephalographic variables and time of reappearance of reflexes in pigs undergoing propofol anaesthesia. MATERIALS AND METHODS: Two experiments have been performed. Five (experiment 1) and sixteen (experiment 2) healthy juvenile pigs were anaesthetised with propofol. In experiment 1, saline, methylphenidate 10 mg/kg or methylphenidate 20 mg/kg was administered intravenously at the end of propofol administration, using a cross-over design. In experiment 2, saline (n = 8) or methylphenidate 20 mg/kg (n = 8) was administered immediately after extubation. In both experiments, physiological parameters, nociceptive withdrawal reflex thresholds, electroencephalographic variables and time of reappearance of reflexes were assessed. Comparison among groups was performed using either the two-way repeated measures ANOVA followed by Bonferroni-Test or the t-test in case of parametric data, and either the Kruskal-Wallis test or the Mann-Whitney Rank Sum test in case of non-parametric data. A p value < 0.05 was considered statistically significant. RESULTS: No clinically relevant changes were observed in both experiments for physiological parameters, nociceptive withdrawal reflex thresholds and electroencephalographic variables. CONCLUSIONS: Methylphenidate does not shorten or modify anaesthesia recovery in pigs, when the sole propofol is administered.

How Is the Nociceptive Withdrawal Reflex Influenced by Increasing Doses of Propofol in Pigs?

The nociceptive withdrawal reflex (NWR) is a physiological, polysynaptic spinal reflex occurring in response to noxious stimulations. Continuous NWR threshold (NWRt) tracking has been shown to be possibly useful in the depth of anesthesia assessment. The primary aim of this study was to describe how propofol modulates the NWRt over time in pigs. Five juvenile pigs (anesthetized three times) were included. An intravenous (IV) infusion of propofol (20 mg/kg/h) was started, and boli were administered to effect until intubation. Afterwards, the infusion was increased every ten minutes by 6 mg/kg/h, together with an IV bolus of 0.5 mg/kg, until reaching an electroencephalographic suppression ratio (SR) of between 10% and 30%. The NWRt was continuously monitored. For data analysis, the time span between 15 min following intubation and the end of propofol infusion was considered. Individual durations of propofol administration were divided into five equal time intervals for each pig (TI1-TI5). A linear regression between NWRt and TI was performed for each pig. Moreover, the baseline NWRt and slopes of the linear regression (b1) were compared among days using a Friedman Repeated Measures Analysis of Variance on Ranks. The NWRt always increased with the propofol dose (b1 = 4.71 ± 3.23; mean ± standard deviation). No significant differences were found between the baseline NWRt and the b1 values. Our results suggest that the NWRt may complement the depth of anesthesia assessment in pigs receiving propofol.

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs.

The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low doses. The secondary aims were to identify associated behavioural effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, an intravenous bolus of 1 mg/kg was administered over 2 min. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 min, followed by an infusion at 0.01 mg/kg/min for 1 h. Blood samples were collected for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. Levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady-state racemic ketamine plasma concentration of 150 ng/mL was 0.028 mg/kg/min. Higher scores for behavioural effects were observed within the first five minutes following bolus administration. The most common behaviours observed were disorientation, head movements and staring eyes. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

Sedline® Miscalculation of Depth of Anaesthesia Variables in Two Pigs Due to Electrocardiographic Signal Contamination.

Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression ratio, raw EEG traces, and its spectrogram were assessed. Physiological parameters and electrocardiographic activity were continuously monitored. In one pig (Case 1), during the administration of high doses of propofol, the Sedline-generated variables suddenly indicated an increased EEG activity while this was not confirmed by observation of either the raw EEG or its spectrogram. In the second pig (Case 2), a similar event was recorded during euthanasia with systemic pentobarbital. Both events happened while the EEG activity was isoelectric except for signal interferences and synchronous in rhythm and shape with the electrocardiographic activity. The suggestion of increased brain activity based on the interpretation of the Sedline variables was suspected wrong; most probably due to electrocardiographic interferences. In pigs, the patient state index and suppression ratio, as calculated by the Sedline monitor, could be influenced by the electrocardiographic activity contaminating the EEG trace, especially during otherwise isoelectric periods (strong EEG depression). Visual interpretation of the raw EEG and of the spectrogram remains necessary to identify such artefacts.

Antinociceptive, Sedative and Excitatory Effects of Intravenous Butorphanol Administered Alone or in Combination with Detomidine in Calves: A Prospective, Randomized, Blinded Cross-Over Study.

(1) Background: The diagnostic and therapeutic procedures performed under sedation or general anesthesia in bovines are numerous. The analgesic drugs that can be legally used are few, making perioperative analgesia challenging. (2) Methods: Calves were administered butorphanol 0.1 mg kg-1 alone (SB) or combined with 0.02 mg kg-1 of a detomidine (DB) IV. The antinociceptive effect (trigeminocervical reflex threshold (TCRt)), as well as the behavioral (sedation and excitation) and physiological (heart and respiratory rate) changes were investigated. Five time windows were defined: BL (30 min pre-injection), T1 (0-30 min post-injection (PI)), T2 (31-60 min PI), T3 (61-90 min PI) and T4 (91-120 min PI). (3) Results: Both groups had a significative increase in TCRt at T1-T4 compared to the BL. The TCRt was significatively higher in DB than in SB at T1, T2 and T4. Heart rate decreased significatively in DB compared to that in BL. Calves were significantly more sedated in the DB group, and significantly more excited in the SB group compared to the BL. (4) Conclusions: Butorphanol alone has a statistically significant antinociceptive effect, but it elicits marked excitation, limiting its clinical applicability under this dosing regimen. The co-administration of detomidine eliminated the excitatory effect and induced consistent sedation and a significantly more pronounced antinociceptive effect.

How is depth of anaesthesia assessed in experimental pigs? A scoping review.

BACKGROUND: Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the use of depth of anaesthesia indicators in this species. METHODS: Medline, Embase and CAB abstract were searched up to September 22nd 2022. No limits were set for time, language and study type. Only original articles of in vivo studies using pigs or minipigs undergoing general anaesthesia were included. The depth of anaesthesia indicators reported in the selected papers were divided in two categories: A, indicators purposely investigated as method to assess depth of anaesthesia; B, indicators reported but not investigated as method to assess depth of anaesthesia. RESULTS: Out of 13792 papers found, 105 were included after the screening process. Category A: 17 depth of anaesthesia indicators were found in 19 papers. Studies were conducted using inhalant anaesthetics as the main anaesthetic agent in the majority of the cases (13/19 = 68.4%), while 3/19 (15.8%) used propofol. The most investigated depth of anaesthesia indicators were bispectral index (8/19 = 42.1%) and spectral edge frequency 95% (5/19 = 26.3%). Contrasting results about the specific usefulness of each depth of anaesthesia indicators were reported. Category B: 23 depth of anaesthesia indicators were found in 92 papers. The most reported depth of anaesthesia indicators were: motor response following a stimulus (37/92 = 40.2%), depth of anaesthesia scores (21/92 = 23.3%), bispectral index (16/92 = 17.8%) and spectral edge frequency 95% (9/92 = 9.8%). CONCLUSION: Results highlight the lack of scientifically valid and reliable indicators to ensure adequate depth of anaesthesia in pigs.

Correlation of Sedline-generated variables and clinical signs with anaesthetic depth in experimental pigs receiving propofol.

Most of currently available electroencephalographic (EEG)-based tools to assess depth of anaesthesia have not been studied or have been judged unreliable in pigs. Our primary aim was to investigate the dose-effect relationship between increasing propofol dose and variables generated by the EEG-based depth of anaesthesia monitor Sedline in pigs. A secondary aim was to compare the anaesthetic doses with clinical outcomes commonly used to assess depth of anaesthesia in this species. Sixteen juvenile pigs were included. Propofol infusion was administered at 10 mg kg-1 h-1, increased by 10 mg kg-1 h-1 every 15 minutes, and stopped when an EEG Suppression ratio >80% was reached. Patient state index, suppression ratio, left and right spectral edge frequency 95%, and outcomes from commonly used clinical methods to assess depth of anaesthesia in pigs were recorded. The best pharmacodynamic model was assessed for Patient state index, suppression ratio, left and right spectral edge frequency 95% in response to propofol administration. The decrease of Patient state index best fitted to an inhibitory double-sigmoid model (including a plateau phase). The increase of suppression ratio fitted a typical sigmoid Emax model. No relevant relationship could be identified between spectral edge frequency 95% values and propofol administration. A large variability in clinical outcomes was observed among pigs, such that they did not provide a reliable evaluation of propofol dose. The relationship between propofol dose and Patient state index/suppression ratio described in the present study can be used for prediction in future investigations. The evaluation of depth of anaesthesia based on common clinical outcomes was not reliable.

Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles.

The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45 min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC-MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%-56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl1 ) and central and peripheral volumes of distribution (V1 , V2 ). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs.

A Survey on the Use of Spirometry in Small Animal Anaesthesia and Critical Care.

The objective was to document the use of spirometry and ventilation settings in small animal anaesthesia and intensive care through a descriptive, open, online, anonymous survey. The survey was advertised on social media and via email. Participation was voluntary. The google forms platform was used. It consisted of eight sections in English: demographic information, use of spirometry in spontaneously ventilating/mechanically ventilated dogs, need for spirometry, equipment available and calibration status, ventilation modes, spirometry displays, compliance (CRS) and resistance (RRS) of the respiratory system. Simple descriptive analyses were applied. There were 128 respondents. Respondents used spirometry more in ventilated dogs than during spontaneous breathing. Over 3/4 of the respondents considered spirometry essential in "selected" (43%) or "most" cases (33%). Multiple devices and technologies were used. The majority of the respondents were not directly involved in or informed about the calibration of their equipment. Of all displays, pressure-volume loops were the most common. Values of CRS and RRS were specifically monitored in more than 50% of cases by 44% of the respondents only. A variety of ventilation modes was used. Intensivists tend to use smaller VT than anaesthetists. More information on reference intervals of CRS and RRS and technical background on spirometers is required.

A Systematic Review of the Methods of Assessment of Gastro-Oesophageal Reflux in Anaesthetized Dogs.

We reviewed the definitions and methods of assessment of gastro-oesophageal reflux (GOR) in anaesthetized dogs. Three databases were used. Titles and abstracts were screened by two of the authors independently. A total of 22 studies was included in the analysis. The definition of GOR implied the presence of fluids not reaching the mouth or nose in the oesophagus in all studies. Most studies considered a change in pH using oesophageal pH meters as the sole method of assessment. Calibration of the pH probe was inconsistently reported. The position of the tip of the oesophageal probe was inconsistent and not always precisely described. The correct positioning in the intended location was verified in a limited number of studies. Some studies considered that GOR had happened for changes in pH below 4.0 or above 7.5 while others considered that GOR had happened when the pH dropped below 4.0 only. Some studies stated that the pH change had to be sustained for a minimum period of time (20 or 30 s) whereas others did not mention any duration. The variability of definitions and methods of assessment of GOR in anaesthetized dogs precludes meaningful comparison of the findings. Re-evaluation and uniformization of the methods appear necessary.

Antinociceptive effects of levomethadone in standing horses sedated with romifidine.

OBJECTIVE: To evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI). STUDY DESIGN: Prospective, randomized, masked, crossover experimental study. ANIMALS: A group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)]. METHODS: Levomethadone 0.1 mg kg-1 or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%-75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05. RESULTS: Horses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration. CONCLUSIONS AND CLINICAL RELEVANCE: A single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α2-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked.

A quick approach for medetomidine enantiomer determination in dog plasma by chiral liquid chromatography-tandem mass spectrometry and application to a pharmacokinetic study.

In the present study, a rapid, sensitive and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of medetomidine enantiomers in dog plasma was developed and validated. The separation and individual quantification of chiral compounds can be a tricky task in LC. This is particularly true when target analytes have a relatively small mass, as is the case with medetomidine, a potent and highly specific α2-adrenoceptor agonist widely used in both human and veterinary medicine. The proposed approach is based on a quick liquid-liquid extraction with ethyl acetate and filtration prior to injection. The optimized mobile phase composition allowed to perfectly separate the two enantiomers of medetomidine in a short chromatographic run time, using a cellulose tris(4-methylbenzoate)-based chiral column. A lower limit of quantification of 0.1 ng/mL was reached for both analytes thanks to the high sensitivity and selectivity of MS/MS and the use of racemic medetomidine-d3 as internal standard prevented potential matrix effect. Linearity was satisfying (R2  > 0.99) over the range 0.1-25 ng/mL, as well as within- and between-session accuracy and precision, both always <15%. This method was also applied with success to a series of samples from a pharmacokinetic (PK) study aimed at comparing dex- and levomedetomidine behaviour after administration of the racemic mixture in dogs. The simple extraction procedure, which allows reduced solvent and time consumption without compromising analytical performances, makes this technique a useful tool for this kind of applications even when small animals are involved, due to the small amount of sample required.

Investigation of selected respiratory effects of (dex)medetomidine in healthy Beagles.

OBJECTIVE: To investigate the effects of sedative doses of intravenous (IV) medetomidine (MED) or dexmedetomidine (DEX) on selected respiratory variables in dogs. STUDY DESIGN: Randomized, blinded, crossover study. ANIMALS: A total of eight healthy adult research Beagles. METHODS: Dogs breathing room air had an electrical impedance tomography belt placed around the chest and were maintained in right lateral recumbency. Respiratory rate (fR) in movements minute-1 (mpm) and changes in thoracic impedance (ΔZ) in arbitrary units (AU) were recorded for 120 seconds before (T0) and exactly 10 minutes (T10) after the administration of IV DEX (10 µg kg-1) or MED (20 µg kg-1), with a minimum washout period of 10 days between treatments. Minute ΔZ (ΔZ˙) was calculated by multiplying median ΔZ with fR. Data are presented as median (interquartile range). Significance for an overall effect of drugs (DEX versus MED) or treatment (T0 versus T10) was quantified with a two-way analysis of variance for repeated measures, followed by, when appropriate, Wilcoxon's signed rank test for each factor. RESULTS: Overall, fR decreased from 26 (22-29) mpm at T0 to 13 (10-21) mpm at T10 (p = 0.003) and ΔZ increased from 1.133 (0.856-1.599) AU at T0 to 1.650 (1.273-2.813) AU at T10 (p = 0.007), but ΔZ˙ did not change [30.375 (23.411-32.445) AU minute-1 at T0 and 30.581 (22.487-35.091) AU minute-1 at T10]. There was no difference between DEX and MED. Most dogs developed a peculiar breathing pattern characterized by clusters of breaths followed by short periods of apnoea. CONCLUSIONS AND CLINICAL RELEVANCE: Both drugs caused a change in breathing pattern, reduction in fR and increase in ΔZ but did not affect ΔZ˙. It is likely that (dex)medetomidine resulted in reduction in fR and increase in tidal volume without impacting minute volume.

Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles.

The objectives were: (1) to compare the antinociceptive activity of dexmedetomidine and medetomidine, and (2) to investigate its modulation by atipamezole. This prospective, randomized, blinded experimental trial was carried out on eight beagles. During the first session, dogs received either medetomidine (MED) (0.02 mg kg-1 intravenously (IV)] or dexmedetomidine (DEX) [0.01 mg kg-1 IV), followed by either atipamezole (ATI) (0.1 mg kg-1) or an equivalent volume of saline (SAL) administered intramuscularly 45 min later. The opposite treatments were administered in a second session 10-14 days later. The nociceptive withdrawal reflex (NWR) threshold was determined using a continuous tracking approach. Sedation was scored (0 to 21) every 10 min. Both drugs (MED and DEX) increased the NWR thresholds significantly up to 5.0 (3.7-5.9) and 4.4 (3.9-4.8) times the baseline (p = 0.547), at seven (3-11) and six (4-9) minutes (p = 0.938), respectively. Sedation scores were not different between MED and DEX during the first 45 min (15 (12-17), p = 0.67). Atipamezole antagonized sedation within 25 (15-25) minutes (p = 0.008) and antinociception within five (3-6) minutes (p = 0.008). Following atipamezole, additional analgesics may be needed to maintain pain relief.

Pharmacokinetic-pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses.

OBJECTIVE: To evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration. STUDY DESIGN: Prospective, experimental, nonrandomized trial. ANIMALS: A total of 10 healthy adult warmblood horses. METHODS: Romifidine (loading dose: 0.08 mg kg-1, infusion: 0.03 mg kg-1 hour-1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic-pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested. RESULTS: A two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33). CONCLUSIONS AND CLINICAL RELEVANCE: Romifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration.

Do the Manual or Computer-Controlled Flowmeters Generate Similar Isoflurane Concentrations in Tafonius?

Introduction: Tafonius is an anesthesia machine with computer-controlled monitor and ventilator. We compared the isoflurane fluctuations in the circuit with manual (MF) or computer-driven (CF) flowmeters, investigated the origin of the differences and assessed whether isoflurane concentration time course followed a one-compartment model. Material and Methods: A calibrated TEC-3 isoflurane vaporizer was used. Gas composition and flows were measured using a multiparametric monitor and a digital flowmeter. Measurements included: (1) Effects of various FiO2 with MF/CF on the isoflurane fraction changes in the breathing system during mechanical ventilation of a lung model; wash-in kinetic was fitted to a compartmental model; (2) Gas outflow at the common gas outlet (CGO) with MF/CF at different FiO2; (3) Isoflurane output of the vaporizer at various dial settings with MF/CF set at different flows without and with reduction of the CGO diameter. Results: (1) The 3% targeted isoflurane concentration was not reached; additional time was required to reach specific concentrations with CF (lowest FiO2, longer time). The exponential course fitted a two-compartment model; (2) Set and measured flows were identical with MF. With CF at 0.21 FiO2, flow was intermittently 7.6 L min-1 or zero (mean total: 38% of the set flow); with CF at 1.00 FiO2, flow was 10.6 L min-1 or zero (mean: 4-5.3 L min-1); with 0.21 < FiO2 < 1.00, combined flow was intermittent (maximum output: 15.6 L min-1); (3) With MF, isoflurane output was matching dial setting at 5 L min-1 but was lower at higher flows; with CF generating intermittent flows, isoflurane output was fluctuating. With the 4 mm diameter CGO, isoflurane concentration was close to dial setting with both MF and CF. With a 14 G CGO, isoflurane concentration was lower than dial setting with MF, higher with CF. Conclusions and Clinical Relevance: Using MF or CF led to different isoflurane fraction time course in Tafonius. Flows were lower than set with CF; the TEC-3 did not compensate for high/intermittent flows and pressures; the CGO diameter influenced isoflurane output.

Colon constipation in horses after sustained-release buprenorphine administration.

OBJECTIVE: To investigate the pharmacological profile and side effects of buprenorphine administered as a sustained-release formulation in horses. STUDY DESIGN: Pilot trial. ANIMALS: A total of four experimental horses, aged 18-27 years and weighing 508-578 kg. METHODS: Buprenorphine (0.1 mg kg-1) was mixed as a freshly prepared sterile solution with a sustained-release drug carrier. It was administered by the subcutaneous (n = 2) or intramuscular (n = 2) route. During the experiment, the horses were closely monitored, equipped with a step counter and blood samples were collected for quantification of buprenorphine in plasma. RESULTS: All four horses developed colon constipation requiring medical therapy, together with increased locomotor activity. One horse, requiring surgical treatment of colon constipation, was euthanized during recovery from anaesthesia for weakness and severe lower airway obstruction. The three other horses recovered fully within 5-7 days. Plasma buprenorphine concentrations were between 1 and 8 ng mL-1 for approximately 48 hours. No local reaction was observed at the injection sites. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of the sustained-release formulation of buprenorphine at a dose of 0.1 mg kg-1 resulted in plasma concentrations compatible with antinociceptive activity for at least 48 hours. The observed severe and undesirable effects of colon constipation and increased locomotor activity definitely preclude clinical use of sustained-release buprenorphine at this dose.

Suspicion of Postanesthetic Femoral Paralysis of the Non-Dependent Limb in a Horse.

A 15-year-old Selle Francais gelding was presented to the equine referral hospital for treatment of a left guttural pouch mycosis previously diagnosed. After induction, the horse was shortly hoisted by all four feet, moved on a padded surgical table, and positioned in right lateral recumbency. In order to reduce the risk of bleeding during surgical manipulation of the carotid and maxillary arteries, a mean arterial pressure between 60 and 70 mmHg was targeted. After surgery, the horse was moved in a padded recovery box keeping the same lateral recumbency. Four unsuccessful attempts were performed, with the horse always returning to sternal recumbency keeping the left hind limb up. At the fifth attempt, performed 120 min after the end of the general anesthesia, the horse stood up correctly but moderate ataxia and absence of weight bearing on the left hind limb were shown. Both the stifle and the fetlock joint were held in a flexed position and could not be extended properly in order to set the foot on the ground, resulting in a very short step. The horse was calm, not sweating, and willing to move; the muscles of the affected limb were relaxed, and the limb was neither warm nor painful at palpation. Occasionally, the horse flexed the affected hind limb in an exaggerated motion with marked abduction. No additional laboratory analyses were performed. Due to a strong suspicion of neuropathy, a sling support was initiated and a supportive bandage associated with flunixine administration was performed until resolution of the symptoms. The horse fully recovered after 3 days. This case report does not clarify the pathogenesis of the possible postanesthetic neuropathy accounted on the non-dependent limb, highlighting the need for future research in this field. Non-dependent limb neuropathy should be an expected problem even after having ruled out the most commonly known causes predisposing to postanesthetic lameness.